There is an increasing awareness that the heritable defects of the five enzymes of the urea cycle may be more common than previously thought. We plan a systematic program to: 1) develop a screening method for the detection of these diseases in susceptible populations, 2) develop a prenatal test for these diseases, 3) develop methods for detection of the heterozygous state so as to describe the mode of inheritance, 4) develop methods of therapy that minimize the requirement for urea synthesis by providing a high calorie, low protein diet supplemented with essential amino acids and their keto analogues, and 5) study the metabolism of urea cycle precursors and intermediates in patients and animal models of these diseases.